rs4149153

Variant names:

• chr12-20898555-C-T
• rs4149153
• NM_019844.4:c.1747+55C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-20898555-C-T
• chr12-20898555-C-A
• chr12-20898555-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019844.4(SLCO1B3):​c.1747+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 819,426 control chromosomes in the GnomAD database, including 265,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41934 hom., cov: 32)
  • Exomes 𝑓: 0.81 (223796 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.533
• Publications: 5 publications found

Genes affected

SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]

SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-20898555-C-T is Benign according to our data. Variant chr12-20898555-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	NM_019844.4	MANE Select	c.1747+55C>T		intron	N/A	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.1747+55C>T		intron	N/A	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.1663+55C>T		intron	N/A	NP_001336849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.1747+55C>T		intron	N/A	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.1747+55C>T		intron	N/A	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.1747+55C>T		intron	N/A	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110711 AN: 151666 Hom.: 41910 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.773

GnomAD4 exome AF: 0.815 AC: 543806 AN: 667642 Hom.: 223796 AF XY: 0.821 AC XY: 289504 AN XY: 352642

African (AFR) AF: 0.517 AC: 8098 AN: 15670

American (AMR) AF: 0.761 AC: 22131 AN: 29078

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 16079 AN: 18354

East Asian (EAS) AF: 0.662 AC: 20158 AN: 30466

South Asian (SAS) AF: 0.907 AC: 45573 AN: 50240

European-Finnish (FIN) AF: 0.670 AC: 30500 AN: 45528

Middle Eastern (MID) AF: 0.865 AC: 2129 AN: 2462

European-Non Finnish (NFE) AF: 0.841 AC: 372948 AN: 443408

Other (OTH) AF: 0.807 AC: 26190 AN: 32436

GnomAD4 genome AF: 0.730 AC: 110781 AN: 151784 Hom.: 41934 Cov.: 32 AF XY: 0.724 AC XY: 53689 AN XY: 74176

African (AFR) AF: 0.524 AC: 21644 AN: 41342

American (AMR) AF: 0.770 AC: 11729 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3046 AN: 3468

East Asian (EAS) AF: 0.666 AC: 3431 AN: 5148

South Asian (SAS) AF: 0.910 AC: 4387 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6847 AN: 10516

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.839 AC: 57021 AN: 67940

Other (OTH) AF: 0.777 AC: 1639 AN: 2110

Alfa AF: 0.822 Hom.: 54507

Bravo AF: 0.730

Asia WGS AF: 0.756 AC: 2595 AN: 3432

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.4
DANN	Benign	0.19
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4149153; hg19: chr12-21051489;